Author:
Garlid Keith D.,Puddu Paolo E.,Pasdois Philippe,Costa Alexandre D. T.,Beauvoit Bertrand,Criniti Anna,Tariosse Liliane,Diolez Philippe,Santos Pierre Dos
Abstract
This study investigates the role of the mitochondrial ATP-sensitive K+ channel (mitoKATP) in response to positive inotropic stress. In Langendorff-perfused rat hearts, inotropy was induced by increasing perfusate calcium to 4 mM, by adding 80 μM ouabain or 0.25 μM dobutamine. Each of these treatments resulted in a sustained increase in rate-pressure product (RPP) of ∼60%. Inhibition of mitoKATP by perfusion of 5-hydroxydecanoate (5-HD) or tetraphenylphosphonium before induction of inotropic stress resulted in a marked attenuation of RPP. Inhibition of mitoKATP after induction of stress caused the inability of the heart to maintain a high-work state. In human atrial fibers, the increase in contractility induced by dobutamine was inhibited 60% by 5-HD. In permeabilized fibers from the Langendorff-perfused rat hearts, inhibition of mitoKATP resulted, in all cases, in an alteration of adenine nucleotide compartmentation, as reflected by a 60% decrease in the half-saturation constant for ADP [ K1/2 (ADP)]. We conclude that opening of cardiac mitoKATP is essential for an appropriate response to positive inotropic stress and propose that its involvement proceeds through the prevention of stress-induced decrease in mitochondrial matrix volume. These results indicate a physiological role for mitoKATP in inotropy and, by extension, in heart failure.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
25 articles.
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